Klotho antiaging protein: molecular mechanisms and therapeutic potential in diseases

Molecular Biomedicine, Год журнала: 2025, Номер 6(1)

Опубликована: Март 22, 2025

Abstract Klotho, initially introduced as an anti-aging protein, is expressed in the brain, pancreas, and most prominently kidney. The two forms of Klotho (membrane-bound soluble form) have diverse pharmacological functions such anti-inflammatory, anti-oxidative, anti-fibrotic, tumour-suppressive etc. membrane-bound form plays a pivotal role maintaining kidney homeostasis by regulating fibroblast growth factor 23 (FGF 23) signalling, vitamin D metabolism phosphate balance. deficiency has been linked with significantly reduced protection against various pathological phenotypes, including diabetic disease (DKD), which major cause chronic leading to end-stage disease. Owing pleiotropic actions klotho, it shown beneficial effects DKD tackling complex pathophysiology reducing inflammation, oxidative stress, well fibrosis. Moreover, protective effect klotho extends beyond other conditions, cardiovascular diseases, alzheimer's disease, cancer, inflammatory bowel liver Therefore, this review summarizes relationship between expression diseases special emphasis on DKD, distinct mechanisms potential exogenous supplementation therapeutic strategy. Future research into could unravel novel treatment avenues for diseases.

Язык: Английский

---

The mechanisms underlying acute myocardial infarction in chronic kidney disease patients undergoing hemodialysis

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 177, С. 117050 - 117050

Опубликована: Июль 4, 2024

Cardiovascular disease (CVD) is a leading cause of death in chronic kidney (CKD). Hemodialysis one the main treatments for patients with end-stage disease. Epidemiological data has shown that acute myocardial infarction (AMI) accounts reason CKD under hemodialysis therapy. Immune dysfunction and changes metabolism (including high level inflammatory cytokines, disorder lipid mineral ion homeostasis, accumulation uremic toxins et al.) during can deteriorate stability atherosclerotic plaque promote vascular calcification, which are exactly pathophysiological mechanisms underlying occurrence AMI. Meanwhile, itself also adverse effects on lipoprotein, immune system hemodynamics, contribute to incidence AMI these patients. This review aims summarize further promising methods prevention treatment undergoing hemodialysis, provide an excellent paradigm exploring crosstalk between cardiovascular system.

Язык: Английский

---

Role of symbiotic microbiota dysbiosis in the progression of chronic kidney disease accompanied with vascular calcification

Frontiers in Pharmacology, Год журнала: 2024, Номер 14

Опубликована: Янв. 5, 2024

Background: Chronic kidney disease (CKD) is now globally recognized as a critical public health concern. Vascular calcification (VC) represents significant risk factor for cardiovascular events in individuals with CKD. It the accessible and precise diagnostic biomarkers monitoring progression of CKD concurrent VC are urgently needed. Methods: The adenine diet-induced rat model was utilized to investigate chronic injury, thoracic aorta, dysregulation biochemical indices. Enzyme-linked immune sandwich assays were employed analyze changes calcification-related proteins. 16S rRNA sequencing performed delineate microbiota characteristics gut blood CKD-afflicted rats. Additionally, transcriptome tissue conducted explore relationship between CKD-associated features alterations function. Results: inhibited body weight gain, led pronounced aorta. both these affected rats exhibited significantly lower alpha diversity distinctive beta than those their healthy counterparts. resulted several indices (including elevated levels creatinine, low-density lipoprotein-cholesterol, sodium, phosphorous, total cholesterol, urea decreased albumin, calcium, lactate dehydrogenase, bilirubin). Moreover, it upregulated factors (bone sialoprotein [BSP], Klotho, fibroblast growth [FGF]-23, sclerostin [SOST]) lipopolysaccharide (LPS). Notably, increased Acinetobacter positively associated calcifications addition positive correlation microbiota. enrichment increases (BSP, FGF-23, SOST), LPS, phosphorous. Furthermore, revealed that correlated majority genes negatively downregulated involved mineral absorption pathway. Conclusion: Our findings, first time, underscore dysbiosis symbiotic microbiota, blood, Particularly, emerges potential its accompanying VC.

Язык: Английский

---

The role of N-methyladenosine modification in acute and chronic kidney diseases

Molecular Medicine, Год журнала: 2023, Номер 29(1)

Опубликована: Дек. 8, 2023

Abstract N 6-methyladenosine (m6A) modification is a kind of RNA in which methylation occurs at the sixth position adenosine RNA, can occur various RNAs such as mRNAs, lncRNAs and miRNAs. This one most prominent frequent posttranscriptional modifications within organisms has been shown to function dynamically reversibly variety ways, including splicing, export, attenuation translation initiation efficiency regulate expression. There are three main enzymes associated with m6A modification: writers, readers erasers. Increasing evidence that onset development kidney disease. In this article, we address important physiological pathological roles diseases (uremia, ischemia–reperfusion injury, drug-induced diabetic nephropathy) its molecular mechanisms provide reference for diagnosis clinical management diseases.

Язык: Английский

---

The pathophysiology and management of vascular calcification in chronic kidney disease patients

Expert Review of Cardiovascular Therapy, Год журнала: 2023, Номер 21(2), С. 75 - 85

Опубликована: Янв. 30, 2023

Introduction Vascular calcification (VC) which is the pathological mineral deposition in vascular system, predominantly at intimal and medial layer of vessel wall, an important comorbidity patients with chronic kidney disease (CKD) leading to significant morbidity mortality while necessitating appropriate treatment. Our review aims provide in-depth analysis current understanding VC.

Язык: Английский

---

Relationship between Serum Indoxyl Sulfate and Klotho Protein and Vascular Calcification in Patients with Chronic Kidney Disease Stages 3–5

International Journal of Endocrinology, Год журнала: 2024, Номер 2024, С. 1 - 7

Опубликована: Фев. 14, 2024

Objective. This study aims to explore the relationships between serum indoxyl sulfate (IS) and Klotho protein levels with vascular calcification in patients chronic kidney disease (CKD) stages 3–5. Methods. From December 2021 January 2023, a total of 108 CKD 3–5 were enrolled this cross-sectional investigation. Demographic information routine clinical biochemistry test results gathered. Serum IS quantified through enzyme-linked immunosorbent assays. Furthermore, multislice spiral computed tomography was employed evaluate calcification. The association or abdominal aorta assessed using univariate analysis logistic regression analyses. Results. With progression stages, creatinine, phosphorus, intact parathyroid hormone (iPTH), IS, aortic exhibited incremental trends, while calcium showed diminishing trend, statistically significant differences ( $P<0.05$ ). Significant observed age, blood calcium, hormone, without id="M2">P<0.05 Logistic demonstrated that advanced high level, low level independent risk factors for id="M3">P<0.05 Conclusion. indicates elevated decreased patients. High

Язык: Английский

---

Metformin reverts aortic calcifications and elastin loss induced by an experimental metabolic syndrome

Endocrine Connections, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Metabolic syndrome (MetS) is associated with osteogenic transdifferentiation of vascular smooth muscle cells (VSMC) and accumulation arterial calcifications (AC). Metformin (MET) inhibits this in vitro. Here, we evaluate the vivo efficacy oral MET to reduce AC a model MetS. 20 young male Wistar rats were divided into 2 groups: one received water, other water plus 20% fructose induce After 14 days, for another 4 weeks, (100 mg/kg/day) was added half each group’s drinking source, thus: C (water), F (fructose), M FM (fructose+MET). Serum adipose tissue collected. Aortas dissected histomorphometric immunohistochemical analysis; ex calcification studies; isolate VSMC measure their alkaline phosphatase activity (ALP), collagen production, extracellular mineralization, gene expression RUNX2 RAGE (receptor AGEs), elastic fiber production. group showed parameters compatible Aortic tunica media from decreased elastic-to-muscular ratio, increased content levels AGEs carboxymethyl-lysine. arches presented tendency higher calcification. ALP, secretion, mineralization RAGE; All these effects reverted by co-treatment (FM group). In vitro, AGEs-BSA upregulated control VSMC, prevented an AMPK-dependent manner. Thus, experimental MetS induces upregulation aortic that curbed treatment MET.

Язык: Английский

---

Risk factors for radial artery calcification in patients with and without uremia

BMC Nephrology, Год журнала: 2025, Номер 26(1)

Опубликована: Янв. 11, 2025

Calcification of the radial artery is one main causes anastomotic stenosis in autogenous arteriovenous fistulas uremic patients. However, pathogenesis calcification still unknown. This study attempted to screen and validate risk factors for vascular patients with uremia. Serum blood were collected tissue samples from obtained 60 uremia or without hemodialysis. General biochemical indicators calcification-related molecules detected via ELISA correlation analysis. In addition, pathological changes evaluated by HE immunohistochemical staining. There differences total calcium, calcium-phosphorus products, allograft inflammatory factor 1 (AIF-1), intact parathyroid hormone (iPTH), vitamin D (VD), fibroblast growth 23 (FGF23) soluble klotho (sKlotho) Furthermore, these are related artery. The expression AIF-1, PTHR1, VDR, FGF23 sKlotho was also increased calcified levels PTH, serum associated further aggravated abnormalities calcium phosphorus maintenance hemodialysis

Язык: Английский

---

Evaluation of Individual Cardiovascular Risk in Pre-Dialysis CKD Patients by Using the Ratio of Calcium–Phosphorus Product to Estimated Glomerular Filtration Rate (Ca × P/eGFR)

Biomedicines, Год журнала: 2025, Номер 13(1), С. 235 - 235

Опубликована: Янв. 19, 2025

Background: Chronic kidney disease (CKD) patients have an increased risk of cardiovascular (CVD), necessitating effective assessment methods. This study evaluates the calcium–phosphorus product (Ca × P) to estimated glomerular filtration rate P/eGFR) ratio as a potential biomarker for predicting CV in pre-dialysis CKD patients. Methods: Eighty-four stages G1–G4, according KDIGO criteria, were classified into CVD (n = 43) and non-CVD 41) groups. Biochemical parameters, including serum creatinine (SCr), blood urea nitrogen (BUN), calcium (Ca), inorganic phosphate (Pi), parathyroid hormone (PTH), alkaline phosphatase (ALP), Ca P, eGFR, P/eGFR ratio, measured calculated. Statistical analyses performed identify predictors evaluate diagnostic reliability risk. Results: Significant differences observed SCr, BUN, eGFR (p < 0.001), 0.007) between Regression analysis indicated significant predictor 0.012, OR 1.206, 95% CI: 1.042–1.395). Receiver Operating Characteristic (ROC) curve revealed AUC 0.751 0.001, 0.645–0.857), with sensitivity specificity method 74.4% 70.7%, respectively. correlations found UA, Ca, Pi, PTH, ALP. Conclusions: The may serve patients, suggesting that its integration routine evaluations could enhance stratification management.

Язык: Английский

---

Association between the aggregate index of systemic inflammation and CKD: evidence from NHANES 1999–2018

Frontiers in Medicine, Год журнала: 2025, Номер 12

Опубликована: Март 10, 2025

Purpose We aimed to investigate the potential association between aggregate index of systemic inflammation (AISI) and chronic kidney disease (CKD). Patients methods This study analyzed data from National Health Nutrition Examination Survey (NHANES) spanning 1999 2018. CKD was defined as either an estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m 2 or presence albuminuria, a urine albumin-to-creatinine ratio (ACR) 30 mg/g higher. Low eGFR is . Multivariate regression analysis, smoothed curve fitting, subgroup analyses were conducted relationship Inflammatory status CKD. The receiver operating characteristic (ROC) analysis used evaluate its ability identify low eGFR. AISI transformed using natural logarithm (Ln) for statistical analysis. Results Of 50,768 recruits, 49.86% male. prevalence 20.31% 8.57%, respectively. Ln-AISI positively associated with (OR = 1.24; 95% CI: 1.19, 1.28) 1.17; CI:1.11, 1.24). Smooth fitting revealed positive Subgroup interaction tests indicated that stratifications did not significantly alter Threshold effect this became more pronounced when exceeded 5.2 (AISI &gt; 181.27). ROC showed had better discrimination accuracy identifying compared other inflammatory indicators [lymphocyte count (LYM), immune-inflammation (SII), platelet-to-lymphocyte (PLR), product platelet neutrophil (PPN)]. Conclusion correlated CKD, potent greater 181.27. Compared indicators, effective in

Язык: Английский

---